Browsing by Subject "Glucagon-like peptide 1"

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Rolle der GPCR-Signaltransduktion bei der Peptidhormonsekretion in neuroendokrinen Zellen im Darm und im Pankreas
(2008) Leicht, Stefanie; Graeve, Lutz
The insulinotropic peptide hormone Glucagon-like peptide-1 (GLP-1) led to intense interest in the use of this peptide for the treatment of patients with type 2 diabetes. The molecular mechanisms of GLP-1 in the β-cells are examined and well understood, whereas the mechanisms leading to GLP-1 secretion in the L-cells are not understood in detail. However the regulation of GLP-1 secretion from intestinal L-cells seems to be similar to the regulation of the insulin secretion in pancreatic β-cells. In the β-cells a number of G-protein coupled receptors influence the insulin secretion and other signal transduction cascades. Due to the fact, that the three G-protein coupled receptors GPR40, GPR119 and GPR120 are expressed in pancreatic β-cells as well as in the intestinal L-cells, the present studies concentrated on the expression and importance of the three receptors and on their intracellular effects in the L-cells and in the β-cells. GPR40, GPR119 and GPR120 are colocalized with GLP-1 in the enteroendocrine L-cells in the rat ileum and colon between the enterocytes. Moreover GPR119 is colocalized with insulin in the pancreatic β-cells. GPR40 and GPR120 are Gαq-coupled receptors, ligands are longchain unsaturated free fatty acids. GPR119 is a Gαs-coupled receptor being activated by lipids like oleylethanolamide. Activation of the three receptors by selective and unselective agonists stimulates GLP-1 secretion and the glucose induced insulin secretion in vitro and ex vivo, whereas GPR119 amplifies the Gαq-induced GLP-1 secretion. Synthetic agonists were able to enhance the fatty acid induced GLP-1 secretion in an additive manner. Glucose also stimulated the GLP-1 secretion in vitro and ex vivo. In L-cells and β-cells it has been shown that GPR40, GPR119 and GPR120 stimulate cell proliferation and inhibit cell apoptosis via different signal transduction pathways in vitro. Hence the present studies make a contribution to the understanding of the importance of GPR40, GPR119 and GPR120 and their signal transduction pathways for the function of the L-cell and the β-cell.